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Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

2014; Lippincott Williams & Wilkins; Volume: 131; Issue: 1 Linguagem: Inglês

10.1161/circulationaha.114.013748

1524-4539

Milton Packer, John J.V. McMurray, Akshay S. Desai, Jianjian Gong, Martin Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor Shi, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Karl Andersen, Juan Luis Arango, J. Malcolm O. Arnold, Jan Bělohlávek, Michael Böhm, S. А. Boytsov, Lesley Burgess, Walter Cabrera, Carlos Calvo, Chen‐Huan Chen, Andrej Dukát, Yan Duarte, Andrejs Ērglis, Michael Fu, Efraín Gómez, Angel Gonzàlez-Medina, Albert Hagège, Jun Huang, Tzvetana Katova, Songsak Kiatchoosakun, Kee‐Sik Kim, Ömer Kozan, Edmundo Bayram Llamas, Felipe Martínez, Béla Merkely, Iván Mendoza, Arend Mosterd, Marta Negrusz‐Kawecka, Keijo Peuhkurinen, Félix José Alvarez Ramires, Jens Refsgaard, Arvo Rosenthal, Michele Senni, Antonio S. Sibulo, José Silva‐Cardoso, Iain Squire, Randall C. Starling, John R. Teerlink, Johan Vanhaecke, Dragoş Vinereanu, Raymond Wong,

Mechanical Circulatory Support Devices

Background— Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results— We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74–0.94; P =0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52–0.85; P =0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P <0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P =0.005), to receive intravenous positive inotropic agents (31% risk reduction, P <0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P =0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro–B-type natriuretic peptide and troponin) versus enalapril. Conclusions— Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01035255.